The present invention relates to a novel composition of matter comprising a specific crystalline form of the sulfate of the cephalosporin derivative known as 7-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[5-(2-hydroxyeth yl)-4-methylthiazoliomethyl]-3-cephem-4-carboxylate.
This cephalosporin derivative is known and is described, for example. in Japanese Patent Application Kokai (i.e. as laid open to public inspection) No. 67483/85 and in European Patent Publication No. 186 463. It has the formula: ##STR1##
The above-mentioned Japanese Patent Application refers to the hydrochloride. hydrobromide, nitrate, phosphate, methanesulfonate and p-toluenesulfonate of the compounds described therein including the compound of formula (I). The aforementioned European Publication refers to the hydrochloride, hydrobromide, phosphate and sulfate of the compounds described therein including the compound of formula (I). The prior art specifications do not refer to the form in which the salts may be obtained, but conventional methods of preparing salts (including the methods referred to in those prior art specifications) would inevitably lead to the amorphous form of the salts. However, the compound of formula (I) and all of its salts so far investigated have been found by us to be so unstable at room temperature that they cannot, in practice, be used, and it has been necessary to find some way of improving the stability of the compound in order for it to be used practically as a drug. Hence, the only forms of this cephalosporin derivative and its salts heretofore known are too unstable to find any practical use.
We have now surprisingly found that a certain specific crystalline form of the sulfate of this compound shows a remarkable and altogether unexpected stability, which makes this cephalosporin derivative, for the first time, a practical proposition for clinical use.